Naloxegol for Opioid-Induced Constipation

Opioid narcotics are ubiquitous therapeutic agents for acute and chronic pain.  In the United States, more than 240 million opioid prescriptions are dispensed per year.  One of the most common sided effects is constipation.  The mechanism of this side effect is the binding of opioid agonists to μ-opioid receptors located in the enteric nervous system.

The recognition of this mechanism has allowed the development of μ-opioid receptor antagonists. A recent study has shown that Naloxegol helps treat constipation related to opioids in patients with noncancer pain (NEJM 2014; 370: 2387-96).  Naloxegol is a pegylated derivative of the μ-opioid receptor antagonist naloxone.  Pegylation limits the ability of naloxegol to cross the blood-brain barrier; hence, the central pain effects of narcotics are not blocked whereas the effects on the enteric nervous system are limited.

This study reported the results of two phase 3, double-blind studies with a combined 1352 participants.  Response to treatment was defined as having ≥3 spontaneous BMs/week and an increase in baseline of ≥1 spontaneous BM/week for ≥9 of 12 week study period and for ≥3 of the final 4 weeks.

Key results:

  • Response to Naloxegol at 25 mg dosing: 44.4% in first study and 39.7% in second study (compared with 29% of placebo treated patients in both studies).
  • Most adverse effects were mild to moderate and included increased abdominal pain, diarrhea, nausea, and flatulence.  Major cardiovascular events were rare and not increased compared to placebo.

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